That
causes shyness? To Lilly Polk, a retired bookkeeper in northern California,
shyness seems like a family trait. Polk, who enjoys crunching numbers
but fears calling customers, has been shy her whole life. Her mother was
shy and so is her adult daughter.

Yet other shy people attribute their timidness to an external cause,
such as having been raised by an overprotective parent or having been
constantly teased by classmates. Many decades of research into the roots
of shyness find truth in each of these homespun theories: nature and
nurture are part of the recipe for shyness. What's new is that geneticists
are finding the first leads to genes that seem to predispose people toward
being shy.

While the research is still in its early stages, it represents a huge
shift in how geneticists study shyness. Until recently, research on the
genetics of shyness (and other behaviors such as aggression and risk-taking)
did not involve hunting for genes per se. Rather, investigators made inferences
about heredity by examining behavior patterns in families, especially
in twins and adopted childrena field called quantitative genetics.
In these studies, researchers attempt to tease apart the influences of
heredity and the environment by comparing behavior in identical and fraternal
twins, for example. Twins generally share the same environmentthey
are raised by the same parents and attend the same schools. Identical
twins share the same genes; fraternal twins share, on average, half their
genes. Thus, if shyness is inherited, it should be seen more often in
both identical twins than in pairs of fraternal twins.

TAKE THE SHYNESS QUIZ

In one of the major twin studies to date, researchers at the University
of Colorado and Pennsylvania State University observed fraternal and identical
twins in their homes and in the laboratory when they were 14 and 20 months
old. Data showed that genetics contributes substantially to the babies'
tendency to cling to their mothers, cry or exhibit other shy behavior
when encountering a stranger, new toys and other novelties. These researchers
and others indicate that genetics constitutes roughly half of the foundation
of shyness.

But which genes are involved? One line of evidence leads to serotonin,
which has numerous functions in the nervous system including an influence
on mood, memory and learning. Irregularities in the expression or control
of serotonin have been linked to depression, anxiety and a variety of
other disorders. Drugs such as Prozac which affect serotonin are
are now widely used in medicine.

In 1996, geneticist Dean Hamer of the National Institutes of Health and
his colleagues reported that they had found an association between the
serotonin transporter gene and neuroticism, a complex of behaviors that
includes depression, low self-confidence, and shyness around strangers.
Hamer reported in Science that adult volunteers who rated high
on the scale of neuroticism tend to have a short version of the serotonin
transporter promoter, a stretch of DNA that controls how much of the serotonin
transporter gets made. Adults who ranked low in neuroticism tended to
have a long version of the promoter.

Both the long and short copies of the gene are functioning, says Hamer.
However, the short version appears to result in less of the serotonin
transporter, and thus less serotonin activity. Hamer called it the "anxiety
gene." Meanwhile, other studies suggest that another gene, DRD4, may also
play a role in traits such as shyness and anxiety. The DRD4 gene codes
for a protein that binds dopamine, another chemical messenger that has
powerful effects in the brain. Again, the DRD4 gene comes in two forms:
a long and a short version.

In a study reported in a recent issue of Molecular Psychiatry,
behavioral scientist Judith Auerbach, of Ben-Gurion University, Beer Sheva,
Israel, said that infants with short copies of the DRD4 gene and serotonin
transporter promoter are less responsive to stimulation and show more
distress during daily routines, compared to infants with different versions
of these genes. Auerbach cautions that her findings do not define a gene
or genes that predispose infants to future shyness. "That will only be
clearer when the infants are older," says Auerbach, who is continuing
to study the behavior of these infants as they grow. It is also interesting
that a number of studies have linked the longer DRD4 gene to novelty-seeking
behavior, just the opposite of being shy.

Feeling Shy

Still to be determined is how having these or other genes associated
with shyness might cause a person to feel shy. Some clues may come
from the extensive literature on the biological basis of shyness. Studies
by Jerome Kagan, of Harvard University, and others by Nathan Fox, of the
University of Maryland, reveal key physiological differences between shy
and non-shy children. When shy children meet a stranger or encounter other
unfamiliar situations, their hearts beat faster and stronger, their muscles
tense, and they secrete higher levels of stress hormones than children
who are not shy. Brain wave patterns also show differences: shy children
have stronger activity on the right side of the frontal lobe. Other children
show just the opposite.

But correlating a gene with any behavior has many limitations. Indeed,
while several teams of investigators have replicated Hamer's results on
the "anxiety gene," other groups have tried, but failed, to confirm them.
The contradictory findings are not surprising, say Hamer and others who
study the genetics of behavior, given the challenges of pinpointing genes
for behavior.

"It's not like you have a gene for 'X'like you have a gene for
eye color," says Louis Schmidt, an assistant professor of psychology at
McMaster University, in Ontario, Canada, "There are probably many genes
and many interactions of genes that contribute to shyness." Any one gene
may account for only a small portion of shyness, perhaps only one or two
percent. Furthermore, each of those genes probably corresponds to a predisposition
to shyness, but does not guarantee that shyness will occur. The gene's
final impact is probably influenced by interactions with other genes as
well as the environment.

Further research may help clarify the genetics underlying shyness. Hamer
and Schmidt, along with Maryland's Nathan Fox, are now screening DNA collected
from several hundred children who have been identified as shy through
intensive behavioral and physiological measures. The researchers are looking
at differences between these children and other children in the genes
that regulate serotonin and dopamine. "We're very excited about the prospects,"
says Hamer. "These [studies] are a matter of fundamental curiosity about
what makes people unique." Even aside from the influence of a person's
mom or dad or first grade teacher, there are aspects of personality that
appear to be rooted in the genes that remain throughout life.